Case 8 -

Solid-Pseudopapillary Tumor of the Pancreas Mary K. Sidawy The George Washington University Washington, DC

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Clinical History A 49-year-old woman presents with abdominal pain. She has a history of pancreatitis with a pseudocyst 19 years ago, presumed secondary to gallstone disease. CT scan shows a suspicious complex cystic mass in the tail of the pancreas. An intraoperative consultation is performed during surgery. Diff-Quik and H&E-stained smears are prepared. (Figures A,B,C). Case 8 - Figure A - Hypercellular smear containing single and loosely cohesive small neoplastic cells. Stripped nuclei are prominent. Hyaline globules and metachromatic stroma are seen within a "rosette" and in the background (Diff-Quik stain, medium power). Case 8 - Figure B - Hypercellular smear containing single and loosely cohesive small neoplastic cells. The nuclei are round to oval with no significant atypia. The cytoplasm is delicate and indistinct (H&E, medium power). Case 8 - Figure C - At high magnification the nuclei show nuclear membrane irregularity and prominent nuclear grooves. Small, distinct nucleoli are noted (H&E stain, high power). Cytology findings Smears show high cellularity and are composed of small cells. The cells have indistinct scant, delicate, and slightly granular cytoplasm. The nuclei are round to oval with indistinct nucleoli. Prominent nuclear grooves and nuclear membrane irregularity are characteristic features. The neoplastic cells are arranged singly, in loosely cohesive clusters and display rosette formation. Stripped nuclei are often noted. The presence of delicate, branching fibrovascular "papillae" is a helpful feature. Neoplastic cells are arranged around these delicate fibrovascular structures. Hyaline globules and metachromatic stroma are seen within the rosettes and in the background. History and Clinical Follow-up The diagnosis of solid-pseudopapillary tumor of the pancreas was rendered during intraoperative consultation. A distal pancreatectomy revealed a 10cm x 6cm x 4.5 cm circumscribed mass within the tail of the pancreas. The cut surface showed solid and cystic areas. The intraoperative diagnosis was confirmed after histological examination of the permanent sections of the resected pancreas. Discussion: Solid-pseudopapillary tumor of the pancreas (SPTP). Solid-pseudopapillary tumor of the pancreas (SPTP)is the latest consensus designation for this distinctive neoplasm of low malignant potential. SPTP is also known by a wide variety of terms including solid and cystic papillary neoplasm, papillary epithelial neoplasm, papillary and solid neoplasm, solid and cystic tumor and papillary cystic tumor. The term SPTP reflects the solid pattern of growth, and the "papillary" appearance. The papillary structures are secondary to ischemic degeneration of the solid tumor. Ischemia also leads to tumor cell dyscohesion and cyst formation. SPTP represents about 1-2% or pancreatic non-endocrine tumors. It is most common in adolescent girls and young women with a mean age of 26 years. Although rare, it does occur in men (7%) of cases. The tumor is one of low-grade malignant potential with the majority of patients showing long-term survival after complete excision. The tumors are slow growing with overall good prognosis. Clinical presentation Incidental during routine examination. Palpable abdominal mass, abdominal discomfort or pain. Radiologically: well circumscribed solid and cystic mass without septa + capsular calcifications (may appear similar to pseudocyst). Gross features Large tumor: mean diameter 10.3cm, frequently in body or tail (64%). Encapsulated, circumscribed with hemorrhage and cystic degeneration. Cytology High cellularity (even with cystic and hemorrhagic changes). Branching papillary fronds of central thin fibrovascular stalks covered by 1-2 layers of cuboidal or cylindrical cells. Uniform, bland cells with round to oval nuclei, finely granular chromatin and one or more small indistinct nucleoli. Cytoplasm, variable, pale, and poorly defined and may have vacuoles. Moderate nuclear irregularity, indentations, infoldings and grooves. Dyscohesive cell aggregates, rosettes-like structures and single cells. Hyaline droplets or cytoplasmic inclusions. Myxoid, metachromatic material in the fibrovascular stalks and in the background. Background foamy histiocytes and/or multinucleated cells, cellular debris, degenerative features (cholesterol cleft, hemorrhage, calcification). Immunohistochemistry Positive for Vimentin, CD10, CD56. Occasionally positive for neurone specific enolase. Negative for cytokeratins. Pancreatic ductal cells, acinar cells, endocrine cells and multipotential stem cells have been postulated as the origin of SPTP although no definitive conclusions have been made. Cytogenetic analysis and molecular studies have revealed few karyotypic abnormalities involving t (13;17), t (11;22) with EWS-FLI 1 fusion. P53 appears to have a minimal role in SPTP and absence of K-ras mutations has been noted. β-catenin mutations have been described leading to the speculation that this impaired adhesion leads to the pseudopapillary appearance. Differential diagnosis: The cytologic findings observed in the intraoperative smears fall within the general category of cellular lesions composed of small uniform cells. The distinction from other small cell neoplasms such as pancreatic endocrine (islet cell) tumor and acinar cell carcinoma need to be entertained. Acinar cell and ductal carcinomas usually are seen as cohesive sheets of pleomorphic atypical cells with a high mitotic rate, without the pseudopapillary pattern of SPTP. Degenerative features such as cholesterol clefts, foamy macrophages and cyst formation favor SPTP. The following summarizes the differential diagnostic cytologic criteria and clues. Pancreatic endocrine tumor (Islet cell tumor) Rarely cystic but is the foremost differential for SPTP due to the overall cellular monotony, loosely cohesive and rosettes arrangement of the neoplastic cells and the somewhat similar demographic profile of the patients. Highly cellular smears composed of small single cells. Plasmacytoid or monomorphic polygonal cells with granular cytoplasm. Nuclei are usually more rounded with salt and pepper chromatin. Synaptophysin strongly positive; Chromogranin positive; CD10 usually negative. NSE is positive in both lesions. Neurosecretory granules by EM (granules have also been described in SPTP). Acinar cell carcinoma More common in men; wide age range. Also circumscribed but less likely to be cystic. Usually cellular with overlapping crowded groups. Solid nests, short cords and numerous acinar structures. Cells have eccentric nuclei with fine chromatin; increased N: C ratio. Variable mitotic rate (in SPTP, mitoses are uncommon to absent). Strongly positive for trypsin (SPTP is trypsin negative or focally positive); positive for cytokeratins (usually negative in SPTP). Ductal carcinoma More common in men; elderly patients. Usually obvious malignant features, except very well-differentiated variants. Cellular smears with clusters of ductal cells showing loss of polarity. Irregular enlarged nuclei and prominent nucleoli. Pancreatoblastoma Patient younger than 10 years old. Aspirates lack pseudopapillary pattern or fibrovascular cores. Tight clusters of epithelial cells in acinar groups with stromal fragments of bland appearing spindle shaped cells. Epithelial cells have granular cytoplasm and round nuclei with finely granular chromatin. Usually express pancreatic enzymes; Vimentin negative. Also given the solid and cystic nature of SPTP, the differential diagnosis should also include cystic pancreatic lesions/neoplasms. The following summarizes the differential diagnostic criteria and clues. Mucinous neoplasms Older women (mean age 49). Usually a thick, mucoid background with tall columnar cells. Mucinous type epithelium lining papillae. Cytoplasmic mucin vacuoles and hyperchromatic nuclei with coarse chromatin. Degenerative features usually absent. Cytology less likely to be diagnostic. Intraductal papillary mucinous neoplasms Older women (mean age 68). Usually thick, mucoid background with tall columnar cells and mucinous type epithelium lining papillae. Cytoplasmic mucin vacuoles, hyperchromatic nuclei, coarse chromatin. Degenerative features usually absent. Cytology less likely to be diagnostic. Microcystic adenomas Older women (mean age 66). Watery aspirates with scant small aggregates of bland flattened cells without papillary structures. Degenerative features usually absent. Pseudocyts Although non-neoplastic, radiologically may be similar to SPTP. Usually solitary. May also have degenerative background. Inflammatory background with few epithelial cells. 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